We propose to develop a system for large-scale production of human immune (type II) interferon for possible future application to clinical studies for therapy of cancer and mechanistic studies. Further, we plan to make the system as efficient as that used for large-scale production and purification of human leukocyte interferon, which is currently being used in clinical trials. Our preliminary data suggest that our objective is reasonable. Using staphylococcal enterotoxin A as inducer, we estimate that we can produce 1.25 x 10 to the 6th power NIH reference units of immune interferon from 500 ml of blood. This is comparable to the yields reported for human leukocyte interferon. We can purify this interferon 5,000-fold to specific activity greater than 10 to the 6th power units/mg protein using a combination of adsorption, hydrophobic, and gel filtration chromatography with approximately 80% yield of starting interferon. In addition to production and purification studies, the mechanism of the antitumor (anticellular) effects of immune interferon will be studied. We will determine the in vitro antitumor (anticellular) effects of the purified immune interferon in a colony system with transformed human cells. Immune interferon treated cells will transfer viral resistance to untreated cells. The transfer phenonemon will be tested for in the anticellular effects of immune interferon. This type of cell-cell interaction may play an important role in the antitumor effects. Recent studies have indicated in the mouse system that immune interferon preparations are 100 times more effective on a dose basis in preventing and controlling osteogenic sarcoma than virus-induced interferon. These animal studies suggest that human immune interferon may prove a much more effective antitumor agent than human leukocyte interferon. It is important, therefore, that the appropriate methodologies be available for large-scale production and purification and that mechanistic studies be done on the anticellular effect. Safety of the produced interferon will be determined in animal studies.